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Toward predictive R-loop computational biology: genome-scale prediction of R-loops reveals their association with complex promoter structures, G-quadruplexes and transcriptionally active enhancers
- Source :
- Nucleic Acids Research
- Publication Year :
- 2018
- Publisher :
- Oxford University Press, 2018.
-
Abstract
- R-loops are three-stranded RNA:DNA hybrid structures essential for many normal and pathobiological processes. Previously, we generated a quantitative R-loop forming sequence (RLFS) model, quantitative model of R-loop-forming sequences (QmRLFS) and predicted ∼660 000 RLFSs; most of them located in genes and gene-flanking regions, G-rich regions and disease-associated genomic loci in the human genome. Here, we conducted a comprehensive comparative analysis of these RLFSs using experimental data and demonstrated the high performance of QmRLFS predictions on the nucleotide and genome scales. The preferential co-localization of RLFS with promoters, U1 splice sites, gene ends, enhancers and non-B DNA structures, such as G-quadruplexes, provides evidence for the mechanical linkage between DNA tertiary structures, transcription initiation and R-loops in critical regulatory genome regions. We introduced and characterized an abundant class of reverse-forward RLFS clusters highly enriched in non-B DNA structures, which localized to promoters, gene ends and enhancers. The RLFS co-localization with promoters and transcriptionally active enhancers suggested new models for in cis and in trans regulation by RNA:DNA hybrids of transcription initiation and formation of 3D-chromatin loops. Overall, this study provides a rationale for the discovery and characterization of the non-B DNA regulatory structures involved in the formation of the RNA:DNA interactome as the basis for an emerging quantitative R-loop biology and pathobiology.
- Subjects :
- 0301 basic medicine
Transcription, Genetic
R-loop
Computational biology
Biology
Genome
03 medical and health sciences
chemistry.chemical_compound
Transcription (biology)
Genetics
Humans
Enhancer
Promoter Regions, Genetic
Gene
030102 biochemistry & molecular biology
Genome, Human
Computational Biology
Promoter
DNA
G-Quadruplexes
Gene Expression Regulation, Neoplastic
030104 developmental biology
Enhancer Elements, Genetic
chemistry
Nucleic Acid Conformation
RNA
Human genome
Erratum
K562 Cells
Subjects
Details
- Language :
- English
- ISSN :
- 13624962 and 03051048
- Volume :
- 46
- Issue :
- 15
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....020644444784f5cdbbe3239f29311597